Exact Non-parametric Confidence Intervals for Quantiles with Progressive Type-II Censoring

It is shown how various exact non-parametric inferences based on order statistics in one or two random samples can be generalized to situations with progressive type-II censoring, which is a kind of evolutionary right censoring. Ordinary type-II right censoring is a special case of such progressive censoring. These inferences include confidence intervals for a given parent quantile, prediction intervals for a given order statistic of a future sample, and related two-sample inferences based on exceedance probabilities. The proposed inferences are valid for any parent distribution with continuous distribution function. The key result is that each observable uncensored order statistic that becomes available with progressive type-II censoring can be represented as a mixture with known weights of underlying ordinary order statistics. The importance of this mixture representation lies in that various properties of such observable order statistics can be deduced immediately from well-known properties of ordinary order statistics.     

Effects of model misspecification on tests of no randomized treatment effect arising from Cox's proportional hazards model

We examine the asymptotic and small sample properties of model-based and robust tests of the null hypothesis of no randomized treatment effect based on the partial likelihood arising from an arbitrarily misspecified Cox proportional hazards model. When the distribution of the censoring variable is either conditionally independent of the treatment group given covariates or conditionally independent of covariates given the treatment group, the numerators of the partial likelihood treatment score and Wald tests have asymptotic mean equal to 0 under the null hypothesis, regardless of whether or how the Cox model is misspecified. We show that the model-based variance estimators used in the calculation of the model-based tests are not, in general, consistent under model misspecification, yet using analytic considerations and simulations we show that their true sizes can be as close to the nominal value as tests calculated with robust variance estimators. As a special case, we show that the model-based log-rank test is asymptotically valid. When the Cox model is misspecified and the distribution of censoring depends on both treatment group and covariates, the asymptotic distributions of the resulting partial likelihood treatment score statistic and maximum partial likelihood estimator do not, in general, have a zero mean under the null hypothesis. Here neither the fully model-based tests, including the log-rank test, nor the robust tests will be asymptotically valid, and we show through simulations that the distortion to test size can be substantial.     

Nonparametric test for checking lack of fit of the quantité regression model under random censoring

The author proposes a nonparametric test for checking the lack of fit of the quantile function of survival time given the covariates; she assumes that survival time is subjected to random right censoring. Her test statistic is a kemel‐based smoothing estimator of a moment condition. The test statistic is asymptotically Gaussian under the null hypothesis. The author investigates its behavior under local alternative sequences. She assesses its finite‐sample power through simulations and illustrates its use with the Stanford heart transplant data.     

Variable screening for survival data in the presence of heterogeneous censoring

Variable screening for censored survival data is most challenging when both survival and censoring times are correlated with an ultrahigh-dimensional vector of covariates. Existing approaches to handling censoring often make use of inverse probability weighting by assuming independent censoring with both survival time and covariates. This is a convenient but rather restrictive assumption which may be unmet in real applications, especially when the censoring mechanism is complex and the number of covariates is large. To accommodate heterogeneous (covariate-dependent) censoring that is often present in high-dimensional survival data, we propose a Gehan-type rank screening method to select features that are relevant to the survival time. The method is invariant to monotone transformations of the response and of the predictors, and works robustly for a general class of survival models. We establish the sure screening property of the proposed methodology. Simulation studies and a lymphoma data analysis demonstrate its favorable performance and practical utility.     

A likelihood based approach for joint modeling of longitudinal trajectories and informative censoring process

We propose a joint modeling likelihood-based approach for studies with repeated measures and informative right censoring. Joint modeling of longitudinal and survival data are common approaches but could result in biased estimates if proportionality of hazards is violated. To overcome this issue, and given that the exact time of dropout is typically unknown, we modeled the censoring time as the number of follow-up visits and extended it to be dependent on selected covariates. Longitudinal trajectories for each subject were modeled to provide insight into disease progression and incorporated with the number follow-up visits in one likelihood function.     

Bayesian Semiparametric Regression for Median Residual Life

Abstract.  With survival data there is often interest not only in the survival time distribution but also in the residual survival time distribution. In fact, regression models to explain residual survival time might be desired. Building upon recent work of Kottas & Gelfand [ J. Amer. Statist. Assoc. 96 (2001) 1458], we formulate a semiparametric median residual life regression model induced by a semiparametric accelerated failure time regression model. We utilize a Bayesian approach which allows full and exact inference. Classical work essentially ignores covariates and is either based upon parametric assumptions or is limited to asymptotic inference in non-parametric settings. No regression modelling of median residual life appears to exist. The Bayesian modelling is developed through Dirichlet process mixing. The models are fitted using Gibbs sampling. Residual life inference is implemented extending the approach of Gelfand & Kottas [ J. Comput. Graph. Statist. 11 (2002) 289]. Finally, we present a fairly detailed analysis of a set of survival times with moderate censoring for patients with small cell lung cancer.     

Using Auxiliary Time-Dependent Covariates to Recover Information in Nonparametric Testing with Censored Data

Murrayand Tsiatis (1996) described a weighted survival estimate thatincorporates prognostic time-dependent covariate informationto increase the efficiency of estimation. We propose a test statisticbased on the statistic of Pepe and Fleming (1989, 1991) thatincorporates these weighted survival estimates. As in Pepe andFleming, the test is an integrated weighted difference of twoestimated survival curves. This test has been shown to be effectiveat detecting survival differences in crossing hazards settingswhere the logrank test performs poorly. This method uses stratifiedlongitudinal covariate information to get more precise estimatesof the underlying survival curves when there is censored informationand this leads to more powerful tests. Another important featureof the test is that it remains valid when informative censoringis captured by the incorporated covariate. In this case, thePepe-Fleming statistic is known to be biased and should not beused. These methods could be useful in clinical trials with heavycensoring that include collection over time of covariates, suchas laboratory measurements, that are prognostic of subsequentsurvival or capture information related to censoring.     

Semiparametric estimation of treatment effect with time-lagged response in the presence of informative censoring

In many randomized clinical trials, the primary response variable, for example, the survival time, is not observed directly after the patients enroll in the study but rather observed after some period of time (lag time). It is often the case that such a response variable is missing for some patients due to censoring that occurs when the study ends before the patient’s response is observed or when the patients drop out of the study. It is often assumed that censoring occurs at random which is referred to as noninformative censoring; however, in many cases such an assumption may not be reasonable. If the missing data are not analyzed properly, the estimator or test for the treatment effect may be biased. In this paper, we use semiparametric theory to derive a class of consistent and asymptotically normal estimators for the treatment effect parameter which are applicable when the response variable is right censored. The baseline auxiliary covariates and post-treatment auxiliary covariates, which may be time-dependent, are also considered in our semiparametric model. These auxiliary covariates are used to derive estimators that both account for informative censoring and are more efficient then the estimators which do not consider the auxiliary covariates.     

A simple exact method for testing hypotheses about the shape parameter of a log-normal distribution

The log-normal distribution is a useful lifetime distribution in many areas. The survival function of a log-normal distribution cannot be expressed in close forms. This makes it difficult to develop exact statistical methods for parameter estimation when censoring occurs. This article proposes a simple and exact method for conducting statistical tests about the shape parameter of a log-normal distribution. Necessary tables are provided based on Monte Carlo simulation. The method can be used for type II censored data. Comparing with existing exact methods, this method uses fewer tables and is easier for calculations.     

A Profile Conditional Likelihood Approach for the Semiparametric Transformation Regression Model with Missing Covariates

We propose a profile conditional likelihood approach to handle missing covariates in the general semiparametric transformation regression model. The method estimates the marginal survival function by the Kaplan-Meier estimator, and then estimates the parameters of the survival model and the covariate distribution from a conditional likelihood, substituting the Kaplan-Meier estimator for the marginal survival function in the conditional likelihood. This method is simpler than full maximum likelihood approaches, and yields consistent and asymptotically normally distributed estimator of the regression parameter when censoring is independent of the covariates. The estimator demonstrates very high relative efficiency in simulations. When compared with complete-case analysis, the proposed estimator can be more efficient when the missing data are missing completely at random and can correct bias when the missing data are missing at random. The potential application of the proposed method to the generalized probit model with missing continuous covariates is also outlined.     

A Permutation Test for Planar Regression

Oja (1987) presents some distribution-free tests applicable in the presence of covariates when treatment values are randomly assigned. The formulas and calculations are cumbersome, however, and implementation of the tests relies on using a x² approximation to the exact null distribution. In this paper a re-formulation of his test statistic is given which has the advantages of ease of calculation, explicit formulas for permutation moments, and allowing a Beta distribution to be fitted to the exact null distribution.     

Exact inference for the two-parameter exponential distribution under Type-II hybrid censoring

Epstein (1954) introduced the Type-I hybrid censoring scheme as a mixture of Type-I and Type-II censoring schemes. Childs et al. (2003) introduced the Type-II hybrid censoring scheme as an alternative to Type-I hybrid censoring scheme, and provided the exact distribution of the maximum likelihood estimator of the mean of a one-parameter exponential distribution based on Type-II hybrid censored samples. The associated confidence interval also has been provided. The main aim of this paper is to consider a two-parameter exponential distribution, and to derive the exact distribution of the maximum likelihood estimators of the unknown parameters based on Type-II hybrid censored samples. The marginal distributions and the exact confidence intervals are also provided. The results can be used to derive the exact distribution of the maximum likelihood estimator of the percentile point, and to construct the associated confidence interval. Different methods are compared using extensive simulations and one data analysis has been performed for illustrative purposes.     

Multiple imputation of a randomly censored covariate improves logistic regression analysis

Randomly censored covariates arise frequently in epidemiologic studies. The most commonly used methods, including complete case and single imputation or substitution, suffer from inefficiency and bias. They make strong parametric assumptions or they consider limit of detection censoring only. We employ multiple imputation, in conjunction with semi-parametric modeling of the censored covariate, to overcome these shortcomings and to facilitate robust estimation. We develop a multiple imputation approach for randomly censored covariates within the framework of a logistic regression model. We use the non-parametric estimate of the covariate distribution or the semi-parametric Cox model estimate in the presence of additional covariates in the model. We evaluate this procedure in simulations, and compare its operating characteristics to those from the complete case analysis and a survival regression approach. We apply the procedures to an Alzheimer's study of the association between amyloid positivity and maternal age of onset of dementia. Multiple imputation achieves lower standard errors and higher power than the complete case approach under heavy and moderate censoring and is comparable under light censoring. The survival regression approach achieves the highest power among all procedures, but does not produce interpretable estimates of association. Multiple imputation offers a favorable alternative to complete case analysis and ad hoc substitution methods in the presence of randomly censored covariates within the framework of logistic regression.     

Estimation on dependent right censoring scheme in an ordinary bivariate geometric distribution

Discrete lifetime data are very common in engineering and medical researches. In many cases the lifetime is censored at a random or predetermined time and we do not know the complete survival time. There are many situations that the lifetime variable could be dependent on the time of censoring. In this paper we propose the dependent right censoring scheme in discrete setup when the lifetime and censoring variables have a bivariate geometric distribution. We obtain the maximum likelihood estimators of the unknown parameters with their risks in closed forms. The Bayes estimators as well as the constrained Bayes estimates of the unknown parameters under the squared error loss function are also obtained. We considered an extension to the case where covariates are present along with the data. Finally we provided a simulation study and an illustrative example with a real data.     

Empirical likelihood inference for general transformation models with right censored data

In this work, we consider empirical likelihood inference for general transformation models with right censored data. The models are a class of flexible semiparametric survival models and include many popular survival models as their special cases. Based on the marginal likelihood function, we define an empirical likelihood ratio statistic. Under some regularity conditions, we show that the empirical likelihood ratio statistic asymptotically follows a standard chi-squared distribution. Through some simulation studies and a real data application, we show that our proposed procedure can work fairly well even for relatively small sample size and high censoring.     

Slope estimation of covariates that influence renal outcome following renal transplant adjusting for informative right censoring

A new statistical model is proposed to estimate population and individual slopes that are adjusted for covariates and informative right censoring. Individual slopes are assumed to have a mean that depends on the population slope for the covariates. The number of observations for each individual is modeled as a truncated discrete distribution with mean dependent on the individual subjects’ slopes. Our simulation study results indicated that the associated bias and mean squared errors for the proposed model were comparable to those associated with the model that only adjusts for informative right censoring. The proposed model was illustrated using renal transplant dataset to estimate population slopes for covariates that could impact the outcome of renal function following renal transplantation.     

Stratified proportional subdistribution hazards model with covariate-adjusted censoring weight for case-cohort studies

The case-cohort study design is widely used to reduce cost when collecting expensive covariates in large cohort studies with survival or competing risks outcomes. A case-cohort study dataset consists of two parts: (a) a random sample and (b) all cases or failures from a specific cause of interest. Clinicians often assess covariate effects on competing risks outcomes. The proportional subdistribution hazards model directly evaluates the effect of a covariate on the cumulative incidence function under the non-covariate-dependent censoring assumption for the full cohort study. However, the non-covariate-dependent censoring assumption is often violated in many biomedical studies. In this article, we propose a proportional subdistribution hazards model for case-cohort studies with stratified data with covariate-adjusted censoring weight. We further propose an efficient estimator when extra information from the other causes is available under case-cohort studies. The proposed estimators are shown to be consistent and asymptotically normal. Simulation studies show (a) the proposed estimator is unbiased when the censoring distribution depends on covariates and (b) the proposed efficient estimator gains estimation efficiency when using extra information from the other causes. We analyze a bone marrow transplant dataset and a coronary heart disease dataset using the proposed method.     

A resampling‐based test for two crossing survival curves

The area between two survival curves is an intuitive test statistic for the classical two‐sample testing problem. We propose a bootstrap version of it for assessing the overall homogeneity of these curves. Our approach allows ties in the data as well as independent right censoring, which may differ between the groups. The asymptotic distribution of the test statistic as well as of its bootstrap counterpart are derived under the null hypothesis, and their consistency is proven for general alternatives. We demonstrate the finite sample superiority of the proposed test over some existing methods in a simulation study and illustrate its application by a real‐data example.